Key points from the evidence

Trastuzumab is a monoclonal antibody licensed for intravenous administration to treat people with breast cancers that show overexpression of the human epidermal growth factor receptor 2 (HER2) protein or HER2 gene amplification. HER2 overexpression has been linked with a poorer outcome in people with breast cancer.

An application for an extension to the product licence for a subcutaneous formulation of trastuzumab (with hyaluronidase as an excipient) to treat HER2-positive early and metastatic breast cancer was filed with the European Medicines Agency in March 2012.

An open-label randomised controlled trial was conducted in 596 women with non-metastatic (clinical stage I–III) HER2-positive breast cancer (the HannaH study). All women received trastuzumab for 24 weeks neo-adjuvant treatment (that is, before surgery) as well as 1 year of adjuvant, post-surgical therapy. This study found that subcutaneous trastuzumab was non-inferior to intravenous trastuzumab for the primary efficacy outcome of pathological complete response (the absence of invasive neoplastic cells in the breast; remaining ductal carcinoma in situ was accepted). It was also not inferior for the co-primary outcome of pharmacokinetic serum trough concentration in pre-dose cycle 8 (before surgery). Pathological complete response has been associated with long-term clinical benefit but there has yet to be a formal validation of it as a surrogate outcome. The analysis for both outcomes was on the per-protocol population: statistical analysis of results in the intention-to-treat population was not reported in the published paper. Data for patient-oriented outcomes, event-free survival and overall survival were not available.

The same proportion of women in both study groups experienced at least 1 severe or worse adverse event. There were numerically more grade 3 and grade 4 events in the intravenous group than in the subcutaneous group, but those that occurred in the subcutaneous group were more likely to be classed as serious, chiefly because women who experienced them were more likely to be admitted to hospital. No phase III trials which compare the intravenous and subcutaneous formulations of trastuzumab in women with metastatic breast cancer have been conducted.

The manufacturer estimates that using subcutaneous instead of intravenous trastuzumab would lead to savings in acquisition costs. Subcutaneous administration of trastuzumab is quicker and less invasive than intravenous administration, and could be done in people's homes or in community settings. This may be preferred by some people and might lead to savings in hospital resources. However, these benefits may not be realised if trastuzumab is combined with other drugs given intravenously, such as taxanes.

Local decision makers will need to consider the available evidence when making decisions about using subcutaneous trastuzumab, in the setting of their local care pathways and usual trastuzumab-containing treatment schedules, and local patients' preferences regarding whether they prefer to be treated at home or in a day hospital. The likely benefits of its use will need to be balanced against the possible risks and the absence of direct patient-oriented outcomes in early breast cancer, and the absence of phase III studies in metastatic breast cancer.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.